Listeria monocytogenes bacteremia developed during treatment of COVID‐19

Key Clinical Message Listeria monocytogenes is an important pathogen in older patients and immunosuppressed patients, often causing bacteremia. Complications resulting from infections other than COVID‐19 must also be considered during COVID‐19 treatment.


| INTRODUCTION
Listeria monocytogenes is a Gram-positive, nonspore-forming, facultatively anaerobic coccobacillus. 1 This important foodborne pathogen is one of the causative organisms in several outbreaks of foodborne disease.L. monocytogenes is an important pathogen in older patients, pregnant women, and immunosuppressed patients, often causing bacteremia and meningoencephalitis. 2 The common symptoms of listeriosis include fever, headache, confusion, diarrhea, and abdominal pain.Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been pandemic in Japan since 2020. 3Patients with risk factors such as advanced age are more likely to develop severe COVID-19. 4owever, multicenter study from the United Kingdom which enrolled total number of 48,902 COVID-19 patients had no case of Listeriosis and we found only once case of co-infected with Listeriosis from Pakistan. 5,6We report a case of L. monocytogenes bacteremia that developed during treatment for COVID-19.

| CASE PRESENTATION
An 82-year-old man was seen at hospital complaining of persistent dyspnea for 4 days.His medical history included sarcoidosis, complete atrioventricular block, diabetes mellitus, prostate cancer, atrial fibrillation, and chronic kidney disease.He was taking prednisolone 5 mg/day for sarcoidosis and edoxaban 15 mg/day to prevent thrombosis and had received three vaccinations for COVID-19.He drank a glass of wine a day and habitually consumed dry-cured ham and cheese.On examination, his body temperature was 35.5°C, pulse rate 72/min, blood pressure 108/55 mmHg, and respiratory rate 24/min, with a saturation of peripheral oxygen (SpO 2 ) of 92% on room air.His lungs were clear on auscultation.
We diagnosed COVID-19 pneumonia of moderate severity and hospitalized him.Infusion therapy with remdesivir (200 mg on Day 1, followed by 100 mg daily to 4 days) and dexamethasone (6 mg once daily for 10 days) and oxygen therapy were started, with ceftriaxone (2 g/ day) administered for potential complications of bacterial pneumonia.Edoxaban, which he had originally been taking internally, was continued to prevent thrombosis.Four days after admission, bloody stools were observed, but the amount was small and not considered urgent.With treatment, his COVID-19 symptoms and SpO 2 level improved, and his body temperature remained at 36°C, but inflammation as indicated by CRP levels did not decrease.Seven days after admission, blood cultures were rerun, and Gram-positive short bacilli were immediately cultured and considered to be L. monocytogenes based on results of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and beta hemolysis on blood agar (Figure 2).We diagnosed Listeria bacteremia and changed to infusion therapy with ampicillin (8 g/day).Contrastenhanced head and trunk CT was performed, along with echocardiography, but no obvious abscess was found.After 42 days of ampicillin treatment, the inflammatory response had decreased, the patient was in good general condition, and he was discharged (Figure 3).

| DISCUSSION
To our knowledge, this is the first case of L. monocytogenes bacteremia co-occurring with COVID-19 in Japan, similar to that reported from Pakistan. 6Russell et al. reported that bloodstream infections were most frequently caused by Escherichia coli and Staphylococcus aureus in immunocompromised COVID-19 patients, but no case with listeria bacteremia was identified from their multicenter cohort study. 5. monocytogenes is an important bacterium in older people and immunosuppressed patients as it can sometimes lead to serious conditions. 2 Because large-scale outbreaks are few, there are many unknowns regarding the route of infection and epidemiological background.However, an outbreak of cases caused by coleslaw in Canada in 1981 proved food to be one source of infection. 7o large-scale outbreaks have occurred in Japan, foodborne listeriosis has been reported. 8The present patient had no common symptoms of L. monocytogenes-related gastroenteritis such as fever, watery diarrhea, nausea, headache, and joint and muscle pains. 9Gastroenteritis typically occurs 24 h after ingestion (ranging from 6 to 240 h) of a large inoculum of L. monocytogenes and usually lasts 2 days.Although the occurrence of bloody diarrhea on the fourth hospital day would not rule out gastroenteritis associated with L. monocytogenes, it would be reasonable to also consider edoxaban.Moreover, common gastrointestinal symptoms of COVID-19 are abdominal pain and diarrhea 4 but rarely bloody stool.
Goulet et al. reported that the incubation period differed significantly based on the clinical form of invasive listeriosis. 10A longer incubation period was observed in pregnancy-associated cases (median: 27.5 days; range: F I G U R E 1 Chest x-ray showed faint infiltrates in the bilateral lungs (A).Chest computed tomography showed bilateral ground glass opacities or consolidations predominantly in the subpleural region (B, C). 17-67 days; interquartile range [IQR]: 20-36 days) than for meningo-encephalitis cases (9 days; days; IQR: 4-13 days) and bacteremia cases (2 days; 1-12 days; IQR: 1-5 days).Thus, bacteremia appearing on the seventh hospital day seemed to be caused by his habitual food intake.Although our patient' s stool was not cultured, Hafner et al. reported that L. monocytogenes is detected in 10% of human stool samples from an independent cohort of 900 healthy asymptomatic donors, which might be applied to our patient due to his eating potentially contaminated products (ham and cheese). 11No cases caused by environmental contamination have occurred in our hospital, including in the high-care unit/intensive care unit, for two decades, so this possibility is considered extremely low.
This case was consistent with several risks for listeriosis as the patient was older, had diabetes mellitus, was undergoing glucocorticoids therapy, and habitually ate cheese and other food items.In addition to the diversification of food, the distribution of cold foods has allowed long-term preservation of foods, which may be one reason why cases of listeriosis have become common in Japan.
Charlier et al. reported that prognostic factors associated with 3-month mortality in patients with bacteremia and neurolisteriosis were ongoing cancer, aggravation of any preexisting organ dysfunction, multi-organ failure, and monocytopenia. 2 Our patient survived despite having two such risk factors (prostate cancer and renal dysfunction).
Listeriosis can affect other organs, with meningoencephalitis being a particularly serious complication. 12ecause our patient showed no disturbance of consciousness and was taking an antithrombotic agent, we did not examine cerebrospinal fluid.Head CT examination was performed at a later date, but no obvious lesions were observed.Penicillin and ampicillin are effective treatments for listeriosis, and their concomitant use with gentamicin is also reported. 13Therefore, we changed from ceftriaxone to ampicillin based on the blood culture results.The patient was discharged from hospital after 6 weeks administration.He has refrained from taking cheese and certain other foods and has experienced no recurrence.
COVID-19 has several risk factors for severe disease, which include older age, male sex, cardiovascular disease, chronic respiratory disease, diabetes, and obesity. 4ur patient also was older, a steroid user, and had diabetes mellitus.Currently, COVID-19 treatment includes antiviral agents (remdesivir, nirmatrelvir/ritonavir, and molnupiravir) and neutralizing antibodies. 14As this patient had COVID-19 pneumonia with respiratory failure, we used both remdesivir, which is approved in Japan, and dexamethasone, which is reported to reduced mortality in hospitalized patients with COVID-19. 15he causes of complications of listeriosis are unclear, but the risk of bacterial infection is present because of the increased use of steroids in COVID-19 treatment.Further, our patient was also at risk of bleeding from his oral antithrombotic medications.We thought that our patient's episode of bloody stools after admission had caused L. monocytogenes, which had been lurking in his intestinal tract, to enter the bloodstream.Furthermore, because COVID-19 is highly infectious, our patient was treated in a private hospital room, the increased stress of not being able to leave his room may have been an additional factor contributing to the gastrointestinal hemorrhage.

F I G U R E 2
Gram stain in blood culture showed Grampositive short bacilli that were isolated and identified as Listeria monocytogenes.F I G U R E 3Clinical course in this case.CTRX, ceftriaxone; Dex, dexamethasone; RDV, remdesivir.